OBJECTIVE:The
aim of the present study was to evaluate the prevalence and factors associated
with bronchopulmonary dysplasia at a neonatal intensive care unit. METHODS: The study was a
cross-sectional study that used secondary
data from premature infants who were born with less than 32 weeks of
gestational age and were admitted to a neonatal intensive care unit.
Chi-square, Mann-Whitney and multivariate tests were used. Significance was set
at p<0.05. RESULTS: A total of 88 premature
infants were included in the study. Bronchopulmonary dysplasia occurred in
27.3% of the infants and was related to having a gestational age below 28 weeks
(OR: 4.80; 95% CI: 1.50-15.34; p=0.008) and a patent ductus arteriosus (OR:
3.44; 95% CI: 1.10-10.76; p=0.034). The group with bronchopulmonary dysplasia
used mechanical ventilation for a longer duration, with a median of 24.5 days
(p<0.0001). At discharge, the corrected and chronological ages were higher
in the group with bronchopulmonary dysplasia (p<0.0001), with respective
medians of 38.4 weeks and 70.5 days. CONCLUSIONS: In tthis
study, the prevalence of
bronchopulmonary dysplasia was high;
the high prevalence was related to extreme prematurity, patent ductus
arteriosus, a longer period under mechanical ventilation and prolonged
hospitalization. The increased survival of infants with low gestational age
makes this disorder a public health issue.

Perinatal medicine and
improvements in neonatal intensive care have led to increased survival of
premature infants with very low birth weights. This benefit is countered by the
higher incidence of bronchopulmonary dysplasia (BPD), which has become a feared
complication in premature infants.(1)

BPD is a chronic pulmonary disease that affects premature
infants and contributes to their morbidity and mortality. Despite substantial
changes in incidence, risk factors and severity after the introduction of new
therapies and mechanical ventilation (MV) techniques, BPD remains common. Its
pathogenesis is multifactorial and includes immaturity, oxygen toxicity,
infection, patent ductus arteriosus (PDA) and poor postnatal nutrition.(2-8)

According to the population under study, the neonatal care and
the diagnostic criteria used, the prevalence of BPD varies from 20 to 40%.(9-11) Knowledge of factors that are associated with BPD development contributes to
its prevention; BPD often results in prolonged hospitalization, which has
consequences for the premature infants, their families and society.(12)

The present study assessed
the prevalence and factors associated with BPD in premature infants in the
Neonatal Intensive Care Unit (NICU) at Hospital São Sebastião in Viçosa (MG),
Brazil.

METHODS

Study characteristics

The study was a cross-sectional study that used secondary data from
premature infants who were admitted to the NICU at Hospital São Sebastião in
the period of January 1, 2008 to December 31, 2010.

The study included premature
infants who were born with less than 32 weeks of gestation. Because of the loss
of monitoring data, infants who died or were transferred to another hospital
before 36 weeks of corrected age were excluded from the study.

The study was approved by the
Human Research Ethics Committee at the Universidade Federal de Viçosa (number
063/2011) and informed consent was waived.

Variables analyzed

The variable "outcome, BPD" was categorized as "yes" or "no" and was
defined as oxygen-therapy dependence at 36 weeks of corrected age, even in
cases that were associated with pneumonia, meconium aspiration,
gastrointestinal abnormalities and heart disease.(13,14)

- Premature infant
characteristics (qualitative): newborn origin (born at another hospital  yes,
no); gender; Apgar < 7 at the 5th minute; Clinical Risk Index for
Babies (CRIB) ≥ 10;(15) gestational age below 28 weeks; small
for gestational age (SGA - weight below the 10th percentile of
Lubchenco curves); infant respiratory distress syndrome (IRDS); PDA; late
sepsis and the use of two or more doses of surfactant (based on clinical,
radiological and/or blood gas parameters). The CRIB score was adopted as a
measure of the severity at admission, which is indicated for premature infants
with an age below 32 weeks; the CRIB is a simple method that is easy to apply
because it is based on record data that are routinely monitored in the first 12
hours after birth;(16)

- Premature infant
characteristics (quantitative): time under MV (according to the actual routine,
based on clinical, radiological and/or blood gas criteria); total period of
oxygen therapy; weight at birth; gestational age at birth (defined by the best
estimate between the ultrasonography before 20 weeks, the last menstrual period
and the clinical examination); age at onset of enteral feeding; age at onset of
parenteral nutrition (PN); age at onset of full diet (150 mL/kg/day);(17-20) age when birth weight was recovered; weight at discharge and corrected and
chronological age at discharge.

Statistical analysis

The sample size was calculated using the Stat Calc from Epi Info
(version 7.0) with a sample power of 80% plus a 95% confidence interval (95%
CI): 84 patients were required.

The relative frequencies,
medians and maximum and minimum values were obtained. For the qualitative
analysis, a Pearson's chi-squared test or a Fisher's exact test was used, and
for quantitative analysis, a Mann-Whitney test was used. A p<0.05 was
considered significant. A backward LR stepwise multiple regression was applied
to explanatory variables that displayed p<0.20, which related them to the
variable "outcome, BPD (yes or no)''. The software Statistical Package for the
Social Sciences (SPSS, version 17.0) was used for the analyses.

RESULTS

In the period of study, 502 patients were admitted to the NICU (47.4%
of the total population since the unit was opened). Of those, 336 were
premature infants (66.9%), and records were found for 293 of the infants. A
total of 43.3% (n=127) of the infants were younger than 32 gestational weeks,
from whom 24,4% (n=31) died before reaching 36 corrected weeks of age. From
those 96 premature infants, eight were excluded from the study because of a
loss of monitoring data (they were transferred to another hospital before 36
weeks of corrected age). Thus, after applying the inclusion and exclusion
criteria, the final sample had 88 patients.

BPD occurred in 27.3% of the population studied (n=24). Maternal
and premature infant characteristics and their association with BPD development
were evaluated.

The maternal variables "age",
"antenatal corticosteroid use", "at least one prenatal appointment",
"twinning", "hypertensive syndrome" and "cesarean delivery" did not differ
between the groups with and without BPD (Table 1).

Regarding the premature infant characteristics, the group with
BPD was related to a gestational age below 28 weeks (p<0.0001), the
occurrence of IRDS (p=0.027), PDA (p=0.001) and late sepsis (p=0.025) (Table 2).

The medians for gestational age were lower in the BPD group than
in the group without BPD (28.0 and 30.1 weeks, respectively; p=0.001). Similar
outcomes were observed with the birth weight medians, which were 1,049 g and
1,356 g, respectively (p=0.002). A delay in the onset of full diet ingestion
was evident in the premature infants with BPD (median of 24.5 days; p=0.042).

Backward LR stepwise multiple regression was applied to
variables showing p<0.20, which included gestational age below 28 weeks,
birth weight, IRDS, PDA, late sepsis, age at onset of full diet, age of
recovered weight and a CRIB score ≥ 10. However, confounding factors for
a CRIB score ≥ 10, age at onset of full diet and recovered weight led to
their removal from the analysis.

The variables related to BPD occurrence that remained in the
final model were gestational age below 28 weeks (OR: 4.80; 95% CI: 1.50-15.34;
p=0.008) and PDA (OR: 3.44; 95% CI: 1.10-10.76; p=0.034).

There were significant differences for the period under MV and
total oxygen therapy (p<0.0001), and there were higher medians for the
period under MV and total oxygen therapy in the BPD group, with values of 24.5
days and 61.0 days, respectively (Table 3).

At the moment of NICU discharge, the variables "weight",
"corrected age" and "chronological age" were higher in the BPD group
(p<0.0001), with medians of 2,667 g, 38.4 weeks and 70.5 days, respectively.
The higher corrected and chronological age at discharge justified the higher
weights of premature infants with the disease, as gestational age and birth
weight were also lower.

DISCUSSION

In the present study, the BPD prevalence of 27.3% was higher than the
prevalence in other studies; previous results have varied from 15.3% to 24%.(14,21,22) However, if the analysis included eight patients transferred back to their
hometowns without oxygen support (therefore likely having no BDP; these
patients were excluded from the sample as were not followed until 36 weeks of
corrected gestational age), the prevalence would be lower, at levels comparable
to the mentioned studies. Thus, BPD as a complication of prematurity remains a
common disease and a major public health problem because there have been
increased rates of infant survival at lower gestational ages.(23)

For the maternal variables analyzed, there were no differences
between the groups; however, the use of antenatal corticosteroid is known to be
protect against BPD.(11) Gestational hypertension also provides some
protection, which is likely related to the birth of more mature premature
infants.(24,25) Furthermore, a cesarean delivery may be related to
induced prematurity when it is necessary to interrupt the pregnancy.(11)

The present study found a higher occurrence of BPD when
prematurity was extreme. Although gestational age is an important predictor of
BPD,(21,26-28) there are other factors that contribute to BPD, as
shown by the association between BPD and IRDS.(11)

The association between PDA and BPD shown in the present study
has been corroborated by other authors,(21,29) although it was not
observed by Tauzin et al.(30) Even with the clinical and surgical
treatment of PDA, Laughon et al.(31) and Kugelman and Durand(29) did not observe a reduction in the occurrence of BPD. Therefore, conservative
clinical measures that aim at PDA prevention should be established, such as
fluid restriction and adequate ventilation support.(29,32)

This study found an association between longer MV duration and
the occurrence of BPD, which has also been found by other authors.(5,12,27,33,34) A reduction in disease incidence has been reported with the decrease in
MV duration.(5,33-38) The increased use of nasal continuous positive
airway pressure (CPAP) is suggested as a protective ventilation strategy that
is an alternative to invasive ventilation, and the practice of early extubation
can lead to reduced MV duration. Authors promote the use of CPAP as the primary
therapy or after surfactant administration.(34-38) However, there has been limited success of CPAP maintenance without the need
for posterior intubation, especially in extremely premature infants.(39)

The risk of BPD development
can be substantially reduced by decreasing MV duration.(5,33) However,
one must consider that prematurity, either alone or when it is associated with
several perinatal complications, can determine the MV duration and the
consequent risk of BPD.(4,27,40,41)

This study has not confirmed the association between BPD and the
feeding practices and nutritional aspects that were evaluated. However, the
authors confirmed that once the disease had developed, the premature infants
required longer durations of ventilation support and hospital stays, which also
suggests greater nutritional inadequacy.(11,28) In this regard,
early nutritional support is important as a preventive measure for BPD,(29) and there should be an emphasis on the adequate supply of enteral feeding, even
with supplementation by parenteral nutrition.(6,42)

The present study highlights the longer duration of hospital
stays in the group who developed BPD. The inherent risks of prolonged
hospitalization result in social and financial costs that have been
corroborated by other authors.(11,28,43)

CONCLUSIONS

The present study has
several limitations related to cross-sectional and single-center studies,
although it contextualizes a period of three years in the assessed unit, which
has been in operation for six years. Because of its characteristics, the
present study is not a cause and effect study but one of association.

Reducing the incidence of prematurity is the most effective way
to alleviate BPD. If premature birth has occurred, we highlight the necessary
dissemination of practices that prevent PDA development and the use CPAP as an
alternative to invasive ventilation; additionally, early extubation should aim
to decrease the duration of MV. Further studies are suggested to encourage the
use of CPAP.